基于泛素-蛋白酶体途径探讨远志散“益气化痰开窍”治疗阿尔茨海默病的科学内涵  

Hypothesis on the Mechanism of Yuanzhi Powder for Treating Alzheimer’s Disease by“Benefiting Qi and Dissolve Phlegm to Open Brain Orifices”via Ubiquitin-proteasome System

作　　者：郭静[1] 李斌[1] 谢沛俊 喻俊榕 郝彦伟 李若楠 Guo Jing;Li Bin;Xie Peijun;Yu Junrong;Hao Yanwei;Li Ruonan(Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China;College of Clinical Medicine,Chengdu University of Traditional Chinese Medicine,Chengdu 610072,China)

机构地区：[1]成都中医药大学附属医院,成都610075 [2]成都中医药大学临床医学院,成都610072

出　　处：《世界科学技术-中医药现代化》2021年第7期2334-2339,共6页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委员会青年科学基金项目(81704024):经UPS蛋白降解途径探讨化痰开窍法抑制AD磷酸化tua蛋白聚集的分子机制,负责人:李斌;成都中医药大学2019年度杏林学者学科人才科研提升计划(QNXZ2019014):化痰开窍法调控血脑屏障防治阿尔茨海默病的生物学机制,负责人:李斌;四川省科技厅应用基础研究项目(2021YJ0435):基于中医膜系理论探讨化痰开窍法调控脑膜淋巴系统促进Aβ内源性清除的机制研究,负责人:李斌。

摘　　要：阿尔茨海默病(Alzheimer′s disease,AD)是一种常见的神经系统退行性疾病,磷酸化Tau蛋白异常聚集所形成的神经纤维缠结(Neurofibrillary tangles,NFTs)是AD的典型病理特征,直接参与AD的发生发展。因此,AD的治疗可从调节磷酸化Tau蛋白异常聚集入手。中医学认为"痰浊"是导致AD发生的重要病理因素之一,"正气亏虚,痰浊蒙窍"是AD的核心病机。"痰浊"与磷酸化Tau蛋白异常聚集密切相关,磷酸化Tau蛋白异常聚集可归属"痰浊"的范畴。化痰开窍与减少磷酸化Tau蛋白聚集在AD的治疗中有不谋而合之处。泛素-蛋白酶体系统(Ubiquitin-proteasome system,UPS)是细胞内蛋白降解的主要途径,参与AD进程中磷酸化Tau蛋白的降解。UPS功能受损是磷酸化Tau蛋白异常聚集和AD发生的重要原因。本文试图从中医"痰"的视角认识磷酸化Tau蛋白异常聚集,探讨中医"痰浊"与现代医学磷酸化Tau蛋白异常聚集的相关性,并从UPS视角提出益气化痰开窍法治疗AD的作用机制假说,推测UPS可能是远志散益气化痰开窍干预AD的主要途径,精确调控UPS可能是未来研究防治AD的新视角,为科学阐释通过调控UPS蛋白降解途径治疗AD的作用机制提供新思路。Alzheimer’s disease(AD)is a common neurodegenerative disease.Neurofibrillary tangles(NFTs)formed byabnormal aggregation of phosphorylated Tau protein are a typical pathological feature of AD,directly involved in theoccurrence and development of AD.Therefore,the treatment of AD can be started by regulating the abnormalaccumulation of phosphorylated Tau protein.According to traditional Chinese medicine,phlegm is one of the importantpathological factors leading to AD.The core pathogenesis of AD is deficiency of vital qi and phlegm gathered in the brainorifice.Phlegm is closely related to abnormal accumulation of phosphorylated Tau protein,which can be classified asphlegm.Traditional Chinese medicine treatment of AD from phlegm may be related to the targeted regulation ofabnormal accumulation of phosphorylated Tau protein.Ubiquitin-proteasome system(UPS)is the main pathway ofintracellular protein degradation and is involved in the degradation of phosphorylated Tau protein in the process of AD.Impaired UPS function can lead to abnormal aggregation of phosphorylated Tau protein and cause AD.This studyattempts to recognize the abnormal accumulation of phosphorylated Tau protein from the perspective of phlegm in TCM,and discuss the correlation between phlegm and abnormal accumulation of phosphorylated Tau protein.From theperspective of UPS,this study puts forward the hypothesis of the mechanism of action in the treatment of AD with themethod of benefiting Qi and dissolve phlegm to open brain orifices,and speculates that UPS may be the main way forYuanzhi Powder to intervene AD.Precise regulation of UPS may be a new perspective for the prevention and treatment ofAD in the future.This study provides a new idea for the scientific explanation of the mechanism of UPS proteindegradation pathway in the treatment of AD.

关 键 词：阿尔茨海默病 泛素-蛋白酶体系统 益气化痰开窍 痰浊 磷酸化TAU蛋白 远志散 

分 类 号：R289.5[医药卫生—方剂学]